The patent application refers to a method of producing a partially cross-linked bone substitute material, mainly of collagen and a mineral component consisting of apatite, tricalcium phosphate (.alpha. and .beta.) and/or hydroxyl apatite and/or calcium phosphate ceramics. A method of producing a bone substitute is described in U.S. Pat. No. 4,516,276 of the same assignee. Extensive clinical studies have been published in the German publication "Zeitschrift fur Orthopadie"121 (1983), pages 115-123, H. Mittelmeier, B.D. Katthagen, from where it follows that an encouraging and satisfying success has been obtained.
These studies further showed that the material, in spite of a further termal treatment and chloric acid vaporization, was still relatively delispescent during clinical insertion into the tissue, in particular while soaking the blood and tissue fluids, and that the generation of bone tissue was not marked enough. Accordingly, a more compact material would be desirable, which further would create a better stimulation of the bone growth.
PCT publication No. W 081/00963 discloses a method of producing a collagen material which, after admixing with finely grained apatite, served as bone substitute material for the above-mentioned studies. As mentioned in said publication, an essential increase in the absorbency and the mechanical strength relative to previously known collagen fleeces has been obtained by subjecting the collagen material to a further heat treatment or a treatment with gaseous halide acids.
From the same publication follows that it was known to improve the physico-chemical properties of collagen and gelatine products on a chemical basis, for example by cross-linking with aldehydes, in particular formaldehyde or glutaraldehyde. It is stated that those methods have the drawback that the thus obtained products are resorbed only very slowly or not at all by the body when implantated and cause inflammations, defense reactions or the production of foreign substance macro cells. The cross-linking of the collagen products with aldehydes has been effected in an exhaustive manner, resulting in completely cross-linked, plastic material like products which are recognized by the organism as foreign substance and thus cause the mentioned harmful reactions. Residual quantities of free aldehyde in the implant are also harmful to the tissue.
The publication Jap. Traumat. Surg. (1982) 99, pages 265-269 of K. Hayashi et al discloses a collagen-hydroxyl apatite preparation, which was freeze-dried after cross-linking. On one hand, relatively finely grained apatite has been used and on the other hand no hint has been given that the quantity of the admixed glutaraldehyde should be such that none of the above-mentioned reactions occurs.